In the study of cellular biology, biochemistry, pharmacology, immunology, and other biological science related fields, it is desirable to study whole, living, individual and small groups of cells, by manipulating and isolating the cells. Thus, it is desirable to provide holding devices having surfaces comprising a multiplicity of pico liter wells so that cells being observed may be isolated from one another in the pico liter wells enabling single cells to be observed.
Heretofore, while holding devices which have substrates with pico liter wells formed in the substrate surface to trap individual cells have been available, it has been difficult to directly observe the cells as precisely as desirable because of optical artifacts caused by the differences between the refractive indices of the medium carrying the cells and the material forming the pico liter wells. These artifacts are caused by the refraction of light passing from the substrate to the cell carrying medium.
Most commonly, aqueous buffers comprised largely of water are used as a medium for carrying cells to be observed. It is therefore desirable to provide pico liter wells in a surface that has optical characteristics as close to that of water as possible, and more specifically, it is desirable to provide a substrate in which pico liter wells can be formed and that has a refractive index very close to or the same as water.